8QA0

Cryo-EM structure of Cx26 solubilised in LMNG - hemichannel classification - NConst conformation

Summary for 8QA0

• Entry DOI: 10.2210/pdb8qa0/pdb
• EMDB information: 18291
• Descriptor: Gap junction beta-2 protein, PHOSPHATIDYLETHANOLAMINE (3 entities in total)
• Functional Keywords: gap junction large pore channel carbon dioxide sensitive, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 338181.02

Authors

Brotherton, D.H.,Cameron, A.D. (deposition date: 2023-08-22, release date: 2024-06-12, Last modification date: 2024-11-20)

Primary citation

Brotherton, D.H.,Nijjar, S.,Savva, C.G.,Dale, N.,Cameron, A.D.
Structures of wild-type and a constitutively closed mutant of connexin26 shed light on channel regulation by CO 2.
Elife, 13:-, 2024

PubMed Abstract: Connexins allow intercellular communication by forming gap junction channels (GJCs) between juxtaposed cells. Connexin26 (Cx26) can be regulated directly by CO. This is proposed to be mediated through carbamylation of K125. We show that mutating K125 to glutamate, mimicking the negative charge of carbamylation, causes Cx26 GJCs to be constitutively closed. Through cryo-EM we observe that the K125E mutation pushes a conformational equilibrium towards the channel having a constricted pore entrance, similar to effects seen on raising the partial pressure of CO. In previous structures of connexins, the cytoplasmic loop, important in regulation and where K125 is located, is disordered. Through further cryo-EM studies we trap distinct states of Cx26 and observe density for the cytoplasmic loop. The interplay between the position of this loop, the conformations of the transmembrane helices and the position of the N-terminal helix, which controls the aperture to the pore, provides a mechanism for regulation.

PubMed: 38829031
DOI: 10.7554/eLife.93686

Experimental method

ELECTRON MICROSCOPY (2.3 Å)